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KMID : 0620920230550061258
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Experimental & Molecular Medicine
2023 Volume.55 No. 6 p.1258 ~ p.1271
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piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination
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Wentao Zhang
Zongtai Zheng
Keyi Wang
Weipu Mao
Xue Li
Guangchun Wang
Yuanyuan Zhang
Jianhua Huang
Ning Zhang
Pengfei Wu
Ji Liu
Haimin Zhang
Jianping Che
Bo Peng
Junhua Zheng
Peter Somers
Xudong Yao
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Abstract
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Accumulating studies have confirmed that PIWI-interacting RNAs (piRNAs) are considered epigenetic effectors in cancer. We performed piRNA microarray expression analysis on renal cell carcinoma (RCC) tumor tissues and paired normal tissues and performed a series of in vivo and in vitro experiments to explore piRNAs associated with RCC progression and investigate their functional mechanisms. We found that piR-1742 was highly expressed in RCC tumors and that patients with high piR-1742 expression had a poor prognosis. Inhibition of piR-1742 significantly reduced tumor growth in RCC xenograft and organoid models. Mechanistically, piRNA-1742 regulates the stability of USP8 mRNA by binding directly to hnRNPU, which acts as a deubiquitinating enzyme that inhibits the ubiquitination of MUC12 and promotes the development of malignant RCC. Subsequently, nanotherapeutic systems loaded with piRNA-1742 inhibitors were found to effectively inhibit the metastasis and growth of RCC in vivo. Therefore, this study highlights the functional importance of piRNA-related ubiquitination in RCC and demonstrates the development of a related nanotherapeutic system, possibly contributing to the development of therapeutic approaches for RCC.
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KEYWORD
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Targeted therapies, Cancer prevention
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